Martinez Bridget, Peplow Philip V
Department of Pharmacology, University of Nevada-Reno, Reno, NV, USA.
Department of Medicine, University of Nevada-Reno, Reno, NV, USA.
Neural Regen Res. 2025 Jun 1;20(6):1681-1695. doi: 10.4103/NRR.NRR-D-23-01588. Epub 2024 Jan 31.
Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in blood- and brain-based materials. From the studies that had validated the preliminary findings, potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p, -30d-5p, -330-5p, -378a-5p, -21-3p, -330-3p, -345-5p in whole blood, miR-19b-3p, -1180-3p, -125a-5p, let-7e-5p in blood plasma, and miR-7-5p, -23b-5p, -142-3p, -221-5p, -370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptor-site binders (drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics (drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and -29c with miR-30e-3p and -526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p, -29a-3p, -106a-5p, -106b-5p, -107, -125a-3p, -125b-5p and of miR-107, -125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p, -107 was found for manic compared to euthymic patients. In two other studies using blood plasma, downregulation of miR-134 was observed in manic patients compared to controls, and dysregulation of miR-134, -152, -607, -633, -652, -155 occurred in euthymic patients compared to controls. Finally, microRNAs such as miR-34a, -34b, -34c, -137, and -140-3p, -21-3p, -30d-5p, -330-5p, -378a-5p, -134, -19b-3p were shown to have diagnostic potential in distinguishing bipolar disorder patients from schizophrenia or major depressive disorder patients, respectively. Further studies are warranted with adolescents and young adults having bipolar disorder and consideration should be given to using animal models of the disorder to investigate the effects of suppressing or overexpressing specific microRNAs.
微小RNA的异常表达与大脑发育和疾病相关，可为双相情感障碍的诊断和预后提供新的生物标志物。我们在PubMed上搜索了双相情感障碍中的微小RNA生物标志物，发现了18篇关于对人类患者进行研究并于2011年1月至2023年6月发表的原始研究文章。这些研究包括对血液和脑组织材料进行微小RNA谱分析。在已验证初步结果的研究中，成人双相情感障碍的潜在候选生物标志物可能有全血中的miR-140-3p、-30d-5p、-330-5p、-378a-5p、-21-3p、-330-3p、-345-5p，血浆中的miR-19b-3p、-1180-3p、-125a-5p、let-7e-5p，以及血清中的miR-7-5p、-23b-5p、-142-3p、-221-5p、-370-3p。有两项研究调查了接受治疗的双相情感障碍患者微小RNA表达的变化。一项研究显示，在包括典型抗精神病药、非典型抗精神病药和苯二氮䓬类药物的治疗4周后，血浆miR-134与基线相比显著增加。另一项研究评估了包括神经递质受体位点结合剂（B类药物）和镇静剂、催眠药、抗惊厥药及镇痛药（C类药物）在内的处方药对微小RNA结果的影响。这两类药物的联合作用增加了miR-219和-29c结果的显著性，miR-30e-3p和-526b*也具有显著性。对微小RNA进行了测试，看它们是否可作为双相情感障碍在躁狂、抑郁和心境正常不同临床状态下的生物标志物。一项研究表明，与对照组相比，躁狂和心境正常的患者全血中miR-9-5p、-29a-3p、-106a-5p、-106b-5p、-107、-125a-3p、-125b-5p以及miR-107、-125a-3p分别上调，且与心境正常的患者相比，躁狂患者中miR-106a-5p、-107上调。在另外两项使用血浆的研究中，与对照组相比，躁狂患者中观察到miR-134下调，与对照组相比，心境正常的患者中miR-134、-152、-607、-633、-652、-155失调。最后，诸如miR-34a、-34b、-34c、-137以及-140-3p、-21-3p、-30d-5p、-330-5p、-378a-5p、-134、-19b-3p等微小RNA分别显示出在区分双相情感障碍患者与精神分裂症或重度抑郁症患者方面具有诊断潜力。有必要对患有双相情感障碍的青少年和年轻人开展进一步研究，并且应考虑使用该疾病的动物模型来研究抑制或过表达特定微小RNA的效果。
